Abstract 4126158: Persistence to once weekly GLP-1 RAs is associated with lower risk of MI, stroke, and 2-point MACE among patients with T2D and ASCVD in the real world.

Introduction: Studies have shown the reduction of CV events in patients with T2D treated with GLP-1 RAs. However, little is known about how persistent use of GLP-1 RA therapy affects CV outcomes in patients with T2D and ASCVD. The objective of this study was to estimate the association between persistent use of once weekly (OW) GLP-1 RAs and 2-point MACE and its components (MI, stroke) in patients with T2D and ASCVD in a real-world setting. Methods: Adult patients with T2D and ASCVD with ≥1 pharmacy claim for OW GLP-1 RAs during Jan 2018-Nov 2022 were identified in the Optum Research Database. The date of the first OW GLP-1 RA claim was defined as the index date. Patients were followed until a CV event occurred or censored. Discontinuation was defined as a ≥60-day gap in supply of OW GLP-1 RAs. All patients were required to be persistent for ≥3 months of follow-up to allow titration of the therapy. CV events of interest include 2-point MACE, MI and stroke. Kaplan-Meier analyses were used to examine risk of CV events by persistent status within 6, 12, or 18 months of follow-up. Cox proportional hazards models with time-varying exposures were used to assess associations between persistent status and MACE, with persistent status of patients updated for each day of follow-up, adjusting for demographic and baseline clinical characteristics. Results: Among a total of 29516 patients, the median follow up duration was 412 days, median persistence was 254 days, and 63.9% of patients (n=18849) were persistent throughout their variable follow up period. Kaplan-Meier analyses indicated risk of 2-point MACE, MI, and stroke was significantly lower in patients who were persistent within 6, 12 or 18 months of follow-up compared to patients who discontinued within 6, 12 or 18 months of follow-up (all p<0.05); longer persistence led to a qualitatively greater risk reduction. Adjusted hazard ratio (95% confidence interval) from Cox regression with time-varying persistence status during the full variable follow up in all patients for risk of 2-point MACE, MI, and stroke associated with persistent use of OW GLP-1 RAs was 0.70 (0.63-0.77), 0.71 (0.62-0.81), and 0.67 (0.57-0.78), respectively. Conclusions: Patients with T2D and ASCVD who were persistent with OW GLP-1 RAs had a lower risk of 2-point MACE, MI, and stroke than those who discontinued the therapy in real-world clinical practice. Longer persistence of OW GLP-1 RAs appeared to provide greater CV benefits.